Irinotecan-Loaded Polymeric Micelles as a Promising Alternative to Enhance Antitumor Efficacy in Colorectal Cancer Therapy

Abstract

Colorectal cancer has been considered a worldwide public health problem since current treatments are often ineffective. Irinotecan is a frontline chemotherapeutic agent that has dose-limiting side effects that compromise its therapeutic potential. Therefore, it is necessary to develop a novel, targeted drug delivery system with high therapeutic efficacy and an improved safety profile. Here, micellar formulations composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2k) containing irinotecan were proposed as a strategy for colorectal cancer therapy. Firstly, the irinotecan-loaded micelles were prepared using the solvent evaporation method. Then, micelles were characterized in terms of size, polydispersity, zeta potential, entrapment efficiency, and release kinetics. Cytotoxicity and in vivo antitumor activity were evaluated. The micelles showed size around 13 nm, zeta potential near neutral (−0.5 mV), and encapsulation efficiency around 68.5% (irinotecan 3 mg/mL) with a sustained drug release within the first 8 h. The micelles were evaluated in a CT26 tumor animal model showing inhibition of tumor growth (89%) higher than free drug (68.7%). Body weight variation, hemolytic activity, hematological, and biochemical data showed that, at the dose of 7.5 mg/kg, the irinotecan-loaded micelles have low toxicity. In summary, our findings provide evidence that DSPE-mPEG2k micelles could be considered potential carriers for future irinotecan delivery and their possible therapeutic application against colorectal cancer.

Poly(amidoamine) Dendrimer/Camptothecin Complex: From Synthesis to In Vitro Cancer Cell Line Studies

“…The differences in hemolysis levels between incubation times were not statistically relevant ( Figure 6 ). Similarly, no hemolytic activity was previously observed in the literature for CTP-loaded nanoparticles and irinotecan-loaded polymeric micelles [ 35 , 36 ]. Regardless of the increasing concentration of the examined system, the level of hemolysis was around 2%.…”

Dual stimuli-responsive polymeric nanoparticles combining soluplus and chitosan for enhanced breast cancer targeting

“…The neutrality in zeta potential can lessen the unfavorable clearance of NPs by mononuclear phagocyte system, enhance blood compatibility, henceforth, anticancer drug can be passively targeted to tumors with greater efficiency. 78…”

“…The neutrality in zeta potential can lessen the unfavorable clearance of NPs by mononuclear phagocyte system, enhance blood compatibility, henceforth, anticancer drug can be passively targeted to tumors with greater efficiency. 78 The PdI values, also provided in Table 1, showed that all CS-SP NPs except those with a 100 : 1 molar ratio have a PdI less than 0.3. In general, PdI below 0.3 implies homogeneity of size distribution in polydispersed phase nano-formulations.…”